Meloxicam is known as (8E)-8-[hydroxy-[(5-methyl-1,3-thiazol-2-yl)amino]methylidene]-9-methyl-10,10-dioxo-10λ6-thia-9-azabicyclo[4.4.0]deca-1,3,5-trien-7-one, it can also be expressed as (4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide). Meloxicam is depicted by the following chemical structure:

Meloxicam is a non steroidal, anti-inflammatory (NSAID) and anti-pyretic drug used to relieve symptoms of arthritis, fever, and can be used as an analgesic for conditions of inflammatory component. It has been developed originally by Boehringer Ingelheim and marketed in Europe as Melox/Movalis or Recoxa brand names for the treatment of rheumatoid arthritis, short term use in osteoarthritis and ankylosing spondylitis. In the United States its marketed as Mobic® for the treatment of osteoarthritis. Meloxicam is manufactured either as a tablet (7.5 and 15 mg dose) or as an oral suspension (7.5 mg/5 ml dose). The form of meloxicam used in the marketed product, Mobic® is the pure form of meloxicam.
Meloxicam has also been used to treat animal target species (dogs, cats, horses, cattle, and pigs) and is marketed worldwide in three forms; injectable solution, oral suspension, and chewable tablets. In the US, meloxicam is licensed for use in dogs as injectable and oral forms, but is only licensed as injectable solution for cats. The Food and Drug Administration (FDA) has specifically approved the use of meloxicam in dogs to reduce the inflammation and pain of joint diseases and muscle injuries.
Meloxicam is a pastel yellow solid, practically insoluble in water, with higher solubility observed in strong acids and bases. It is very slightly soluble in methanol. Meloxicam has an apparent partition coefficient (log P)app=0.1 in n-octanol/buffer pH 7.4. Meloxicam has pKa values of 1.1 and 4.2.
Enhancement of meloxicam's low aqueous solubility has been the subject of many publications, by using different solvents (see Seedhar et al, AAPS Pharma Sci. Tech. 2003; 4(3) or salt formation (Choi et al, EU J. Pharm and Biopharm. 65 (2007) 99-103) or complexing with metals (Cini et al, J. Chem. Soc. Dalton Trans, 2002, 1888-1897) Preparation of different crystalline ploymorphic forms of meloxicam are disclosed in the literature, see for example U.S. Pat. No. 6,967,248 and application 2006/0025408 A1. In addition, dissolution improvements of meloxicam are also disclosed in U.S. Pat. No. 6,869,948 and WO 99/09988.
Generally, these approaches have involved different polymorphic and salt forms as well as some solid state formulations which sometimes involve generation of certain salt forms, or complexing with metal ions. Such approaches might not be desirable for particular uses, such as parenteral, owing to their inherent lack of stability, acidity and possible toxicity.
Because of the limitations related to the low aqueous solubility of pure meloxicam, there is a need to develop novel forms of meloxicam that have improved physico-chemical properties including aqueous solubility, which can be formulated for use in various delivery routes, including parenteral and oral administration.
Another limitation for the pain relief drug, meloxicam is that it takes a long time to achieve the desired plasma concentration and start reliving pain. The mean peak plasma concentration Cmax for meloxicam is achieved within four to five hours under fasted conditions, indicating prolonged drug absorption which might be influenced by the rate of dissolution. Therefore enhancing the rate of dissolution could lead to shortening Cmax and a quicker onset of pain relief. This is a clear clinical benefit for patients.
These limitations have been tackled by generating novel crystalline forms of meloxicam that includes cocrystals, salts, and solvates (e.g. hydrates and mixed solvates as well as solvates of salts), and mixtures of thereof. The rate of dissolution has been improved and more rapid onset achieved in a rat model.